It is known, for example, in the automated clinical chemistry analyzer art, to utilize liquid handling probes for moving liquid samples and/or reagents among various containers. Typically, liquid handling probes include an open-ended pipetting probe coupled to an automatically-controlled motor-driven syringe-type pump. The probe is lowered into liquid held in a container and a volume of liquid is drawn into the probe by operating the syringe-type pump. The probe is withdrawn from the container and is moved to a position above or within a second container such as a reaction cuvette or cell. Once so positioned, the syringe-type pump is operated again to dispense liquid from the probe into the reaction cell.
A common problem associated with liquid handling probes is carryover. Carryover occurs when, for example, a first reagent is transferred by a probe from a reagent storage container to a reaction cell and, during the next liquid transfer operation, a second different reagent is transferred by the same probe from a second reagent container to the reaction cell. Traces of the first reagent may remain in or on the probe and be carried over to and contaminate the second reagent as it is drawn into and expelled from the probe during the second transfer operation. Such carryover can result in errors in the analysis of samples, a particularly troubling result where the samples are human body fluid samples used in the evaluation and/or treatment of various diseases or disorders.
In order to reduce carryover, it is known to wash the exterior of a probe by dipping the contaminated end portion of the probe into a wash cell filled with a suitable wash liquid, such as deionized water. The wash liquid may be circulated through the wash cell and thus around the exterior of the probe to more thoroughly cleanse the probe exterior. Similarly, it is known to flow wash liquid through the probe. Preferably, the wash liquid is segmented by entrained gas bubbles that tend to scrub the probe interior surface as the bubbles pass, further enhancing the removal of carryover substances.
Several approaches have been utilized for entraining scrubbing gas bubbles in the wash liquid that flows through the probe. One approach has been to repeatedly insert and remove the open end of the probe into wash liquid as the wash liquid is being aspirated by the probe. This produces a number of gas bubbles that are drawn into the probe which are then expelled from the probe into a suitable wash cell or receptacle.
Another known approach is to inject gas bubbles into the wash liquid as it flows through a conduit leading to the probe. Pressurized gas is supplied to a solenoid operated valve which is in turn connected to the conduit carrying the wash liquid. While the wash liquid flows through the conduit, a signal is applied to the valve to rapidly cycle the valve on and off. Each on-off cycle introduces a gas bubble into the wash liquid flow. The gas bubbles are carried by the wash liquid flow to and through the probe, producing the desired scrubbing action.
However, both of these bubble generating techniques approaches have drawbacks. Mechanically cycling the end of a probe into and out of a wash liquid to thereby aspirate gas bubbles is time consuming and limits the size and number of bubbles that may be introduced into the probe. Consequently, probe washing may be compromised, resulting in increased carryover from one transfer operation to the next.
The bubble injection approach, on the other hand, requires an electronic drive circuit that controls the valve. Any changes in gas bubble size or number must be controlled by varying the frequency and duty cycle of the pulsed signal applied to the valve, thereby increasing the complexity of the electronic control circuitry. In any event, most such valves can operate at no more than 100 cycles per second, thus limiting the number of bubbles injected into the liquid flow to 100 bubbles/second.
The bubble injection approach also requires frequent replacement of the solenoid valve. Such a valve may be required to cycle almost 200,000 times during a typical operating day of an automated analyzer. Solenoid valves of the type used in these bubble injection applications have at most a ten million cycle life. Thus, the valves must be replaced at least every two months. Each replacement is expensive and requires that the analyzer be shut down, a problem where the analyzer is one of the primary analytical tools in a hospital clinical chemistry laboratory.
Furthermore, the solenoid valve or the conduit connecting the valve to the wash liquid conduit holds a volume of liquid that is not directly in the wash liquid flow path. This liquid volume represents a dead volume in which reagents or samples drawn into the probe may become trapped, substantially reducing the effectiveness of the wash liquid and gas bubbles. Gas bubbles can also become trapped in the dead volume. Because the gas bubbles are compressible as compared to liquid, the metering accuracy of the liquid delivered by the syringe-type pump can be adversely influenced.
Thus, there is a need for a simple bubble generator which can rapidly inject bubbles into a wash liquid flow. The bubble generator should be reliable and easily adjustable to vary bubble size and spacing while eliminating the electronic circuitry required to operate the rapid cycling valve described above. Furthermore, it is desirable to eliminate or substantially reduce dead volume present in prior art systems.